| What is purpose of vaccination? | To expose the immune system to the components of the microbe and induce memory and a protective secondary immune response, in order to provide:
Prophylactic protection of individuals (mainly): avoid infection or decrease illness severity, decrease infectivity
Post-contact protection of individuals (rarely)
Decrease of disease incidence and protection of the society |
| What are required properties of vaccine? | Safety, Minimal side effects
Efficacy against infection or disease, wide coverage of mutants
Lasting protection
Practical considerations: Feasibility, Cost, Stability, Ease of administration |
| What are vaccines? | Immunogenic, non pathogenic preparations, naturally derived from the wild microorganism or genetically engineered or synthetized to mimic - or to instruct the body to produce- parts of the microbe
Required components include: at least 3 : One B epitope capable of activating B cells or CD8+ T cell epitope activating Tc cells and one CD4+ T cell epitope activating Th, and one PRR receptor agonist activating Dc maturation |
| What are immune responses caused by vaccine? | Humoral (B epitope binds Ig on naive B cells which in turn goes to Th2 which releases cytokines and attaches B cell via CD40L and TCR, activating further more B cells to produce Ab against infection)
Cellular (CD8+ epitope binds Dc and Dc binds Tc, maturing in CTL via cytokines which is then active to kill infected cells via CD28 and TCR) |
| What are important considerations in vaccine development and delivery? | Biology of the pathogen: Virulence and Infectivity, Number of serotypes, potential for mutation, Presence or absence of animal hosts
Characteristics of the vaccine: Stability, safety, reactogenicity, Lasting protective potential: Type of elicited immune response
Logisitics: Production (cost, scale-up…), transport (cold chain), storage, Target population, Trust/hesitancy, field operation (healthcare, campaigns, accessibility |
| What is the balance needed in vaccines? | Safety and Efficacy |
| What are some examples of microorganisms and their types of vaccines? | . |
| What are characteristics of attenuated vs inactivated vaccines? | . |
| What are polio vaccines? | . |
| What are some vaccines based on purified macromolecules? | . |
| What are general characteristics of vaccines based on purified macromolecules? | Advantages: no risk of infection, non reactogenic, better targetting than whole microorganism
Disadvantages: poorly antigenic, need addition of adjuvants to reach acceptable immunogenicity |
| How is selection of adjuvants? | Adjuvant: a substance added in the vaccine that potentiates or modulates the immune response to the antigenic components
Not needed in attenuated, inactivated and recombinant vectors vaccines
Needed in purified proteins, peptides and polysaccharides vaccines
Can be natural (PAMP) or synthetic. Are usually TLR agonists that drive dendritic cell maturation
Other roles: delay of vaccine breakdown (emulsions, mineral salts… ), recruitment of leukocytes
Are the focus of the most recent developments in vaccinology
Modulate qualitatively the immune response : TH2 (humoral) or TH1 (cellular) |
| What are bacterial vaccines based on purified toxoids? | Exotoxins of Clostridium tetani and Corynebacterium diphtheriae are responsible of their pathogenicity
Toxoids are modified non pathogenic exotoxins
Neutralizing anti-toxoid antibodies are efficient in preventing intoxication
Toxins enter cells via cellular receptors, then dissociate releasing active chain which poison cells, protected by Ab blocking the toxin. |
| What are bacterial polysaccharides vaccines? | Capsular polysaccharides (PS) contribute to the virulence of certain bacteria (resistance to phagocytosis)
Anti-PS antibodies
Neutralize bacteria binding to epithelium
activate C’ and macrophages: opsonisation
Vaccine against Streptococcus pneumoniae
Streptococcus pneumoniae causes pneumococcal
pneumonia. Complications: meningitis
Vaccine made of 23 different polysaccharides: Pneumovax 23 or PPSV23 given to people over 65 year old
Vaccine against Neisseria meningitidis
Neisseria meningitidis causes bacterial meningitis
Vaccine made of capsular polysaccharides |
| How are polysaccharides coupled to proteins vaccines? | Limitations of PS vaccines: Unable to activate TH cells
Humoral T-independent response, too low before the age of 2 years
IgM antibodies: no phagocyte opsonisation
Low affinity
Solution = Conjugated vaccine: PS and protein
The protein acts as a carrier
Induction of TH and T-dependent IgG humoral response
Vaccine against Haemophilus influenzae Group B
Haemophilus influenzae Group B is the leading cause of meningitis in children under 5
Vaccine made of polysaccharides coupled to a carrier protein
Provides efficient protection of the newborn |
| What are some examples of polysaccharide conjugated to protein vaccines? | Hib vaccine: Polysaccharides conjugated to a protein carrier
• The polysaccharide (PS) alone may activate B in a Tindependent manner, without memory
• PS conjugated to a carrier protein (tetanus or diphtheria toxoid) induces a T-dependent antibody response with memory
Vaccine against hepatitis B virus
History:
HB virus discovered in 1965 (Australia Antigen)
1st vaccine (1969): inactivated virus purified from serum of infected individuals
2nd vaccine (1986): recombinant protein prepared by genetic engineer |
| How was Hep B recombinant vaccine? | Preparation and composition of the vaccine:
Cloning of the gene encoding the HBsAg in yeast cells
Purification of HBsAg from lysed cells
Addition of an adjuvant to the vaccine preparation
(aluminium hydroxyde = alum)
Commercial names :
Engerix B, Recombivax HB (Merk); ….
Comvax: combined HBV and Hib vaccine
Efficacy: Induces production of protective anibodies |
| How is vaccine against HPV? | HPV: Naked ds
DNA viruses of the papovavirus family that cause warts
More than 200 HPV serotypes, of which 40 may be sexually transmitted
Serotypes mainly involved in genital warts and cervix cancer: 16 and 18
Major serotypes of common warts: 6 and 11
Replication proteins : E
Capsid proteins: L1 (external ) L2 (internal)
Vaccine is empty virus-like particle (only capsid proteins given after using yeast cell as place to replicate) |
| What are available vaccines against HPV? | Gardasil:
Quadrivalent vaccine (6, 11, 16, 18) made of pseudo-viral particles : capsid protein L1
Approved by the FDA in June 2006
Recommended for young girls and boys, age 11-12 (3 doses). Catch-up until 26 years, in sexually inactive women
Cervarix:
Bivalent vaccine (16, 18)
Approved by the FDA in October 2009
Recommanded to girls only, 11-12 years old (3 doses). Catch-up till 26 years |
| What are vaccines based on recombinant vectors? | When the live microorganism is still too virulent and purified proteins are poorly immunogenic, these proteins are expressed by another live microorganism, which is non pathogenic, even for immunocompromized recipients
Genes encoding vaccine candidate antigens are introduced in an attenuated virus or bacterium that becomes a vector. It replicates within the host and expresses the gene product against which an immune response is desired
Examples of vectors :
Bactera: Vibrio cholerae, Salmonella typhiTy21A, Shigella flexneri and Listeria monocytogenes (all attenuated)
Viral : vaccinia, canarypox virus, adenovirus, measles |
| How is rota virus live attenuated vaccine? | Rotaviruses are responsible of most fatal diarrheas in infants
Naked RNA viruses: 3 protein shells, an outer capsid, an inner capsid and an internal core, surround the 11 segments of ds RNA.
The outer capsid proteins are neutralization antigens :
VP4 (P) is the viral attachment protein: defines the P serotype (11 P serotypes. Main one is P1[8]
VP7 (G) protein is the major outer capsid protein. Defines the G serotype
Two live attenuated vaccines are available
Rotarix: monovalent human vaccine. One serotype: P1[8]G1
Rotareq: pentavalent recombinant bovine-human vaccine. Four viruses express human G of serotypes and bovine P or vice versa |
| What were the main considerations for COVID vaccine? | . |
| What were the factors for success and challenges in COVID vaccine? | Success: Rapid genome sequencing [1 month], open access data, experience [from 2003 SARS], more knowledge of pathogen [SARS-COV and spike protein], advanced vaccine technology
Challenges: No adequate animal model preclinical evaluation, intended primary target population [frontline healthcare pros, people >60 yrs, chronic diseases], profitability |
| What is mechanism of action of Astrazenca, J&J and Gamaleya vaccines of COVID? | Replication-defective viral vector contains the target antigen-encoding gene ->
The viral vector is injected in muscle cells ->
It directs target protein synthesis in the cell. Replication defective vector disintegrates afterwards ->
Large numbers of target protein molecules are produced by the cell and recognized by B and T cells ->
The immune system makes protein specific antibodies and Cytotoxic T cells and mounts specific memory |
| How is mechanism of action of RNA-based vaccines Moderna and Pfizer COVID? | mRNA encoding the target protein only, enclosed in a lipid nanoparticle
The mRNA is injected in muscle cells ->
It is translated in target protein , then disintegrates afterwards ->
Large numbers of target protein molecules are produced by the cell and recognized by B and T cells ->
The immune system makes protein-specific antibodies and Cytotoxic T cells and is ready to make more if it encounters the virus |
